Ngu Abanda, MSc, PhD
Nominated From: University of Hawai’i
Research Site: Centre Pasteur of Cameroon
Research Area: Infectious disease & Immunology
Primary Mentors: Dr. Vivek Nerurkar and Dr. Rose Leke
Research Project
An assessment of humoral and cellular immunity against yellow fever in HIV+ and HIV- children vaccinated during infancy
Vaccination of residents in yellow fever endemic countries and visitors travelling to these areas is a straightforward way of preventing yellow fever [1, 2]. In endemic countries, the yellow fever vaccine (YFVac) is routinely administered to infants at 9-12 months of age. Prior to 2014, vaccination at 9-12 months of age was followed by a booster dose every 10 years. In 2014, the World Health Assembly and the Centre for Disease Control adopted the recommendation to discontinue the 10-year boosting on the basis that a single dose confers long-lasting immunity[3]. This recommendation was made without supporting evidence [4] for infants receiving vaccine at 9-12 months of age or in HIV+ persons [2, 3]. Infants vaccinated at 9-12 months age may not develop an immune response similar to adults or may lose immunity more rapidly [5]. A recent serosurvey found that although ~95% of infants developed neutralizing antibodies to yellow fever virus 4wks post-vaccination, by year 6 post-vaccination, ~50% of these infants no longer had any detectable neutralizing antibodies [6]. It would be expected that in the absence of neutralizing antibodies (absence of protection), more yellow fever cases would be reported but that is not the case. This raises the question: does the vaccine induce any long-lasting immune response in infants vaccinated at 9-12 months and are neutralizing antibodies the best correlate to assess this long-lasting protection? Especially, as it has been observed with some vaccines that some vaccinated individuals without measure of neutralizing antibodies remain protected [7]. We propose to characterize the yellow fever vaccine induced humoral (B cells) and cellular (T cell) immune response over time in infants. We hypothesize that the yellow fever vaccine administered at 9-12months elicits a polyfunctional initial and long-lasting antibody and T cell response and that measuring neutralizing antibodies only cannot define this immune response. Specifically, we propose to Aim #1. Determine the presence and persistence of IgG (including IgG subclasses) and IgM antibodies to yellow fever virus in these infants before vaccination to 11-15 years after vaccination. Aim #2. Determine the presence and persistence of neutralizing antibodies to yellow fever virus in these infants before vaccination to 11-15 years after vaccination. Aim #3. Determine the presence of yellow fever specific T cells and T cell response in these infants 7-15 years post vaccination. To investigate our hypothesis, we would use archived biological samples (plasma, Whole blood PBMCs) collected in the PEDIACAM study [8] (ethical approvals No 2021/10/1399/CE/CNERSH/SP) in Cameroon. The PEDIACAM study is a prospective cohort of infants born live to HIV+ and HIV- mothers, included between 2007 – 2011 mostly during their first week of life and followed to date. These children received YFVac at 9-12months of age. Plasma, sera, and subsequently whole blood samples from these infants were archived.
Research Significance
At present, the yellow fever vaccine is the only effective measure for preventing yellow fever. Unfortunately, to date, it remains uncertain if vaccinated infants who receive a single dose at 9-12 months of age will develop a long-lasting immunity. This study will provide key information on the vaccine induced immune response and its persistence in both HIV- and HIV+ infants who received the vaccine at 9-12 months of age.
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